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Elderberry

Materia Medica

Elderberry

Sambucus nigra

immunerespiratory

Elderberry (Sambucus nigra) — an antiviral berry used for influenza and upper respiratory infections, best at the first sign of a cold.

Work in progress Updated May 2019

What Is Elderberry?

Elder is an invasive tree spread throughout most of the world.

It can be found in cold climates like Canada and Scandinavian countries, as well as tropical areas in Central and South America, Southeast Asia, and Australia.

Elder trees are even frequently found in remote areas like the Pacific Islands.

Elder has many uses, especially for upper respiratory infections for its antitussive and antiviral activity.

As an antiviral, it has a relatively narrow range of efficacy, which is specific to enveloped viruses like influenza, and will only have a potent effect in the early stages of viral infection. Elder is highly effective for early-stage viral infection and one of the best herbs to keep around in the event of early signs of cold or flu.

What Is Elder Used For?

Elder is primarily used in the acute stage of respiratory infections. It has the unique ability to structurally inhibit the reproductive cycle of the influenza virus. Used in the early stages, it can prevent the infection from spreading.

Elder is also used for its ability to interact with the central nervous system. For this effect, elder is often used for nerve-related pain.

Traditional Uses

The use of elder dates back a very long time. Evidence of elder seeds, pollen, and dried fruits have been found at a Bronze Age archaeological site in Tuscany (Italy) 12Reference 12Mariotti-Lippi et al. · 2010Palaeovegetational reconstruction based on pollen and seeds/fruits from a bronze age archaeological site in Tuscany (Italy), a Neolithic site in the French Alps 13Reference 13Martin et al. · 2008Plant economy during the Neolithic in a mountain context: The case of “Le Chenet des Pierres” in the french Alps (Bozel-Savoie, France), and Durankulak site the Black Sea coast and north-eastern Bulgaria.

Elder is used in Ayurvedic medicine, but not in depth. Its berries are used primarily as a diuretic and aperient, while the bark as a hydragogue, cathartic and anti-epileptic.

In traditional Chinese medicine, elder (known as “mao gu xiao”; Sambucus formosana or Sambucus chinensis) is used rarely to treat liver disease. It’s considered to be a warm bitter, useful for dispelling blood stasis.

In Indonesia, elder (Sambucus javanica) is used for pain relief, beri beri, and jaundice.

In Western herbal medicine, elder is most commonly used to treat sore throats and as a purgative or emetic. It’s also used to treat wounds (the leaves mainly), or as a diuretic (whole plant).

Elder was commonly combined with herbs like yarrow or boneset in the treatment of cold and flu.

Botanical Information

There are about 30 different species of elder, 3 of which are most commonly used as medicine. The common names for these species include blue elder (Sambucus nigra), red elder (Sambucus racemosa), and white elder (Sambucus australasica).

Phytochemistry

Elder fruit and flower carry several hundred compounds, but the medicinally important ones fall into a few families. The deep colour of the berry comes from anthocyanins — chiefly cyanidin-3-sambubioside and cyanidin-3-glucoside, which together with their 5-glucosides make up over 98% of total anthocyanin content. The dominant flavonol is quercetin-3-O-rutinoside (rutin), and the antiviral/emetic activity tracks to a set of ribosome-inactivating lectins such as nigrin b and the related ebulin 1 11,15,18Reference 11Christensen et al. · 2008Selection of elderberry (Sambucus nigra L.) genotypes best suited for the preparation of elderflower extracts rich in flavonoids and phenolic acidsReference 15Mikulic-Petkovsek et al. · 2014Investigation of anthocyanin profile of four elderberry species and interspecific hybridsReference 18Girbes et al. · 2004Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria.

Flavonol glycosides (rutin plus the kaempferol and isorhamnetin rutinosides) account for ~90% of total flavonoids, and two caffeoylquinic acids — 5-O-caffeoylquinic acid (chlorogenic acid) and 1,5-di-O-caffeoylquinic acid — for ~70% of the phenolic acids. The fruit also supplies ~1% triterpenoids (notably ursolic acid), polyphenols, and vitamins A, B6 and C 11,15Reference 11Christensen et al. · 2008Selection of elderberry (Sambucus nigra L.) genotypes best suited for the preparation of elderflower extracts rich in flavonoids and phenolic acidsReference 15Mikulic-Petkovsek et al. · 2014Investigation of anthocyanin profile of four elderberry species and interspecific hybrids.

Constituent Summary

Anthocyanins and flavonols are given as mg per 100 g fresh fruit (cyanidin-3-glucoside equivalents); ranges are wide across genotype, ripeness and drying. RIP/lectin content is documented qualitatively. Entries marked No Data are reported without a figure 11,15,18,21Reference 11Christensen et al. · 2008Selection of elderberry (Sambucus nigra L.) genotypes best suited for the preparation of elderflower extracts rich in flavonoids and phenolic acidsReference 15Mikulic-Petkovsek et al. · 2014Investigation of anthocyanin profile of four elderberry species and interspecific hybridsReference 18Girbes et al. · 2004Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteriaReference 21Jiménez et al. · 2015ReviewEbulin from dwarf elder (Sambucus ebulus L.): a mini-review.

Anthocyanins
Grouped by class · 4 compounds
Anthocyanin4 compounds2 with data
AnthocyaninCyanidin-3-sambubioside~122–269 mg/100g (fresh)
AnthocyaninCyanidin-3-glucoside~205–481 mg/100g (fresh)
AnthocyaninCyanidin-3-sambubioside-5-glucosideNo data
AnthocyaninCyanidin-3,5-diglucosideNo data
Flavonols
Grouped by class · 3 compounds
Flavonoid3 compounds1 with data
FlavonoidQuercetin-3-O-rutinoside~15–170 mg/100g (fruit)
FlavonoidKaempferol-3-O-rutinosideNo data
FlavonoidIsorhamnetin-3-O-rutinosideNo data
Phenolic acids
Grouped by class · 2 compounds
Phenolic Acid2 compounds1 with data
Phenolic Acid5-O-Caffeoylquinic acid~70% of phenolic acids (with 1,5-di-)
Phenolic Acid1,5-di-O-Caffeoylquinic acidNo data
Triterpenoids
Grouped by class · 1 compound
Triterpene1 compound1 with data
TriterpeneUrsolic acid~1% total triterpenoids (fruit)
Ribosome-inactivating proteins & lectins
Grouped by class · 3 compounds
Protein3 compoundsno data
ProteinNigrin bNo data
ProteinEbulin 1No data
ProteinEbulitinsNo data

What’s the Deal with Elder’s Toxicity Claims?

A group of compounds found in elder called lectins are closely related to the common rat poison — ricin.

Lectins are essentially proteins that can bind with sugars. If lectins like ricin get into the cells, they can interact with our ribosomes (the organelle that does most of the manufacturing of proteins and various other compounds).

The common name given to lectins like ricin that stop the ribosomes from working is referred to as “Ribosome-Inactivating Proteins” or RIPs for short.

RIPs are also thought to be protective against viruses and predators, as well as a way for the plant to store nitrogen.

Several RIPs have been isolated from black elder 18,19,20Reference 18Girbes et al. · 2004Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteriaReference 19Stirpe · 2004Ribosome-inactivating proteinsReference 20Lapadula et al. · 2013Revising the taxonomic distribution, origin and evolution of ribosome inactivating protein genes.

Similar lectin-compounds can be found in other medicinal plants with similar uses (antiviral), and limitations (emetic) — Phytolacca americana (Phytolacca antiviral protein or PAP).

There are three types of RIPs: Type 1, type 2, and type 3. 19,20Reference 19Stirpe · 2004Ribosome-inactivating proteinsReference 20Lapadula et al. · 2013Revising the taxonomic distribution, origin and evolution of ribosome inactivating protein genes.

Both ebulin and ricin are type two RIPs.

How Elder Lectins Are Different from Ricin

Despite structural similarities, elder isn’t as toxic as ricin — and it’s not as toxic as we once thought.

The LD50 of ebulin 1 was 250 mg/kg, compared to ricin’s 0.023 µg/kg (intraperitoneal) and 0.0075 µg/kg (intravenous) 22Reference 22He et al. · 2010AnimalRicin toxicokinetics and its sensitive detection in mouse sera or feces using immuno-PCR — that’s a huge difference. You would essentially need more than 9000 times the dose of ebulin 1 compared to ricin to reach the same toxic dose.

There are some exceptions.

RIPs such as ebulin f and SELfd are toxic and resist breakdown in the stomach — leading to gastrointestinal irritation and upset.

The solution to this problem is to heat it before using it. Heating makes these RIPs vulnerable to breakdown by pepsin in the stomach, neutralizing the toxic effects of ebulin f. 21,25Reference 21Jiménez et al. · 2015ReviewEbulin from dwarf elder (Sambucus ebulus L.): a mini-reviewReference 25Jimenez et al. · 2013Isolation and molecular characterization of two lectins from dwarf elder (Sambucus ebulus L.) blossoms related to the Sam n1 allergen.

Clinical Applications

Elder is a great antiviral herb, especially for Influenza and some of the other enveloped viral species if used at the early stages of infection.

Cautions & Safety

Elder is an emetic, especially in preparations that contain fresh plant material (unheated). If nausea occurs, dial back the dose. Contrary to popular belief elder is NOT poisonous. Emetics are frequently misinterpreted to be dangerously poisonous.

Elder is thought to decrease the effectiveness of morphine.

Contraindications

  • Small children
  • Caution advised with larger doses

References

  1. Zakay-Rones, Z., Varsano, N., Zlotnik, M., Manor, O., Regev, L., Schlesinger, M., & Mumcuoglu, M. (1995). Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. The Journal of Alternative and Complementary Medicine, 1(4), 361-369. [in vitro]
  2. Chen, C., Zuckerman, D. M., Brantley, S., Sharpe, M., Childress, K., Hoiczyk, E., & Pendleton, A. R. (2014). Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC veterinary research, 10(1), 24. [in vitro]
  3. Mascolo, N., Capasso, F., Menghini, A., & Fasulo, M. P. (1987). Biological screening of Italian medicinal plants for anti‐inflammatory activity. Phytotherapy research, 1(1), 28-31.[in vitro]
  4. Yeşilada, E., Üstün, O., Sezik, E., Takaishi, Y., Ono, Y., & Honda, G. (1997). Inhibitory effects of Turkish folk remedies on inflammatory cytokines: interleukin-1α, interleukin-1β and tumor necrosis factor α. Journal of Ethnopharmacology, 58(1), 59-73. [in vtro]
  5. Harokopakis, E., Albzreh, M. H., Haase, E. M., Scannapieco, F. A., & Hajishengallis, G. (2006). Inhibition of proinflammatory activities of major periodontal pathogens by aqueous extracts from elder flower (Sambucus nigra). Journal of periodontology, 77(2), 271-279. [in vitro]
  6. Abuja, P. M., Murkovic, M., & Pfannhauser, W. (1998). Antioxidant and prooxidant activities of elderberry (Sambucus nigra) extract in low-density lipoprotein oxidation. Journal of Agricultural and Food Chemistry, 46(10), 4091-4096. Link. [in vitro]
  7. Murkovic, M., Adam, U., & Pfannhauser, W. (2000). Analysis of anthocyane glycosides in human serum. Fresenius’ journal of analytical chemistry, 366(4), 379-381. [in vitro].
  8. Serkedjieva, J., Manolova, N., Zgórniak‐Nowosielska, I., Zawilińska, B., & Grzybek, J. (1990). Antiviral activity of the infusion (SHS‐174) from flowers of Sambucus nigra L., aerial parts of Hypericum perforatum L., and roots of Saponaria officinalis L. against influenza and herpes simplex viruses. Phytotherapy Research, 4(3), 97-100. [in vitro]
  9. Konlee, M. (1998). A new triple combination therapy. Positive health news, (17), 12. [case report]
  10. Ulbricht, C., Basch, E., Cheung, L., Goldberg, H., Hammerness, P., Isaac, R., … & Weissner, W. (2014). An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration. Journal of dietary supplements, 11(1), 80-120. Link. [review article]
  11. Christensen, L. P., Kaack, K., & Fretté, X. C. (2008). Selection of elderberry (Sambucus nigra L.) genotypes best suited for the preparation of elderflower extracts rich in flavonoids and phenolic acids. European Food Research and Technology, 227(1), 293-305. Link. Other.
  12. Mariotti-Lippi, L.; Bellini, C.; Mori, S. Palaeovegetational reconstruction based on pollen and seeds/fruits from a bronze age archaeological site in Tuscany (Italy). Plant. Biosyst. 2010, 144, 902–908. [OTHER]
  13. Martin, L.; Jacomet, S.; Thiebault, S. Plant economy during the Neolithic in a mountain context: The case of “Le Chenet des Pierres” in the french Alps (Bozel-Savoie, France). Veg. Hist. Archaeobot. 2008, 17, s113–s122. [OTHER]
  14. Marinova, E.; Atanassova, J. Anthropogenic impact on vegetation and environment during the
    Bronze Age in the area of Lake Durankulak, NE Bulgaria: Pollen, microscopic charcoal,
    non-pollen palynomorphs and plant macrofossils. Rev. Palaeobot. Palynol. 2006, 141, 165–178. [OTHER]
  15. Mikulic-Petkovsek, M.; Schmitzer, V.; Slatnar, A.; Todorovic, B.; Veberic, R.; Stampar, F.; Ivancic, A. Investigation of anthocyanin profile of four elderberry species and interspecific hybrids. J. Agric. Food Chem. 2014, 62, 5573–5580. [Chemical profiling].
  16. Ding, M.; Feng, R.; Wang, S.Y.; Bowman, L.; Lu, Y.; Qian, Y.; Castranova, V.; Jiang, B.H.; Shi, X. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J. Biol. Chem. 2006, 281, 17359–17368.
  17. Parikh, B.A.; Tumer, N.E. (2004). Antiviral activity of ribosome inactivating proteins in medicine. Mini Rev. Med. Chem. 2004, 4, 523–543.
  18. Girbes, T.; Ferreras, J.M.; Arias, F.J.; Stirpe, F. Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria. Mini Rev. Med. Chem. 2004, 4, 461–476.
  19. Stirpe, F. Ribosome-inactivating proteins. Toxicon 2004, 44, 371–383.
  20. Lapadula, W.J.; Sánchez Puerta, M.V.; Juri Ayub, M. Revising the taxonomic distribution, origin
    and evolution of ribosome inactivating protein genes. PLoS One 2013, 8, e72825.
  21. Jiménez, P., Tejero, J., Cordoba-Diaz, D., Quinto, E. J., Garrosa, M., Gayoso, M. J., & Girbés, T. (2015). Ebulin from dwarf elder (Sambucus ebulus L.): a mini-review. Toxins, 7(3), 648-658. Link. [review article].
  22. He, X.; McMahon, S.; Henderson, T.D.; Griffey, S.M.; Cheng, L.W. Ricin toxicokinetics and its sensitive detection in mouse sera or feces using immuno-PCR. PLoS One 2010, 5, e12858. [Animal study]
  23. Iglesias, R.; Citores, L.; Ferreras, J.M.; Pérez, Y.; Jiménez, P.; Gayoso, M.J.; Olsnes, S.; Tamburino, R.; di Maro, A.; Parente, A.; et al. Sialic acid-binding dwarf elder four-chain lectin displays nucleic acid N-glycosidase activity. Biochimie 2010, 92, 71–80.
  24. Vimr, E.; Lichtensteiger, C. To sialylate, or not to sialylate: that is the question. Trends Microbiol. 2002, 10, 254–257.
  25. Jimenez, P.; Cabrero, P.; Basterrechea, J.E.; Tejero, J.; Cordoba-Diaz, D.; Girbes, T. Isolation and molecular characterization of two lectins from dwarf elder (Sambucus ebulus L.) blossoms related to the Sam n1 allergen. Toxins 2013, 5, 1767–1779